Ammonium Toxicity in Bacteria

Although an excellent nitrogen source for most bacteria, ammonium was—in analogy to plant and animal systems—assumed be detrimental to bacteria when present in high concentrations. In this study, we examined the effect of molar ammonium concentrations on different model bacteria, namely, Corynebacterium glutamicum, Escherichia coli, and Bacillus subtilis. The studied bacteria are highly resistant to ammonium. When growth was impaired upon addition of molar (NH₄)₂SO₄ concentrations, this was not caused by an ammonium-specific effect but was due to an enhanced osmolarity or increased ionic strength of the medium. Therefore, it was concluded that ammonium is not detrimental to C. glutamicum and other bacteria even when present in molar concentrations.     

Compromised Chemical Toxicity in Year-Weathered Soils: Implications for Compromised Toxicity Factors

With contaminated terrestrial sites always being multiple decades old before they first submit to health risk assessments for humans and ecological receptors, there is great opportunity for soils to elicit markedly lesser chemical toxicity than would be expected. Soil aging and weathering foster various physico-chemical processes that reduce the toxic potency or bioavailability of sequestered chemicals. Because only brand new and unadulterated chemicals with seemingly maximum potencies are used in animal dosing that supports toxicity factor derivation, measured chemical concentrations in soil can be misleading, producing exaggerated risk and hazard outcomes. We sought to determine the extent to which toxicity reduction occurs in experimentally amended soils, working with large soil volumes exposed to the unimpeded ambient condition for a calendar year. A broad toxicity testing matrix for two chemicals (i.e., multiple test species, endpoints, effect level concentrations, and soil types), found species’ responses in contaminated soils to be indistinguishable from those in control soil 80% and 98% of the time for the inorganic and organic compounds used, respectively; a case in point was lead with a soil concentration of 11,000 mg/kg. The results suggest that incorporating a toxicity reduction term is an indispensable task when deriving toxicity factors.     

益母草注射液小鼠急性毒性和Beagle犬重复给药毒性试验研究

通过小鼠单次给药急性毒性试验和Beagle犬重复给药毒性试验,评价益母草注射液(YMC)的安全性。用半数致死剂量法对小鼠进行急性毒性试验,观察小鼠的死亡情况和急性毒性症状,用Bills法计算半致死剂量(LD50)。将32只Beagle犬根据体质量、性别随机分为YMC 240.99 mg·kg~(-1)、120.50 mg·kg~(-1)、60.25 mg·kg~(-1)组和0.9%氯化钠注射液对照组,每组8只。静脉滴注给药,每周给药6 d,连续180 d,停药恢复30 d。对Beagle犬进行临床症状、体质量、心电图、血液学、血液生化学、血清电解质、尿液及组织病理学等检查。YMC小鼠静脉给药LD50为845.64 mg·kg~(-1),急性毒性症状主要表现为跳跃、烦躁、嗜睡、活动减少、阵挛性抽搐、眼球突出、尿失禁。重复给药毒性试验,Beagle犬出现呈剂量反应趋势的流涎、呕吐症状,未见肝、肾毒性,其余各项检测指标也均未见与药物毒性相关的明显异常。YMC小鼠静脉给药LD50相当于临床拟用剂量的394.6倍,YMC重复给药毒性试验对Beagle犬的安全剂量为120.50 mg·kg~(-1),相当于临床拟用剂量的56.2倍。提示YMC具有较高的安全性。     

Bilirubin Toxicity in Hepatoma Cells

BILIRUBIN is present in toxic concentrations in foetuses and premature infants with haemolysis due to blood group incompatibility¹. Hyperbilirubinaemia in the neonate has been associated with irreversible nuclear damage in the brain and other tissues^2,3 and experimental evidence suggests that bilirubin interferes with oxidative phosphorylation^4,5. We have shown that bilirubin inhibits the growth of cells which share with developing tissues the ability to derive an appreciable part of their energy from extramitochondrial processes.     

Acute Zinc Toxicity in Haemodialysis

A country patient on home haemodialysis suffered acute nausea, vomiting, and fever during dialyses when she used water stored in a galvanized tank. She subsequently was found to have severe anaemia with raised plasma and erythrocyte zinc concentrations. Intercurrent hospital haemodialyses and subsequent home dialyses with deionized water were symptom-free.Experimental haemodialyses of dogs against small concentrations of zinc showed a disproportionate rise in plasma zinc and possible uptake of zinc by the liver.     

Commentary on the Role of Maternal Toxicity on Developmental Toxicity

Maternal mammalian toxicity impacts prenatal development, with general systemic maternal toxicity, from reduced weight gain to morbidity, causative for reduced fetal weights/litter and increased fetal variations (especially skeletal)/litter, but not, in the author's opinion, for increased fetal malformations, reduced litter sizes or full litter losses. Increased fetal malformations are likely due to exposure to specific chemicals which alter specific maternal functions at critical point(s) in pregnancy, typically exaggerated effects from higher doses by drugs under development with known, desired pharmacological effects. Malformations can also be from genetic/epigenetic alterations, specific altered proteins, molecular pathways, etc. Full litter losses are triggered by the mother and are rare in rats. Information to inform maternal (and developmental) toxicity includes ovarian corpora lutea counts, uterine implantation profile, degree of litter reduction (if present), timing and extent of maternal toxicity relative to those of adverse embryofetal effects, etc. The view of maternal toxicity as confounding results in in vivo developmental toxicity studies, worldwide concerns about increased research animal usage, increasing time, labor, costs, and new software and hardware sophistication all drive the interest in development, validation, and performance of in vitro/in silico assays. These assays are fast, inexpensive, responsive to animal use concerns and amenable to mechanistic questions. The strength of these in vitro/in silico assays is considered by many to be the absence of the maternal organism/placenta. These assays inform mechanism and hazard, but NOT risk. The Environmental Protection Agency currently estimates that these new assays are approximately 70% accurate versus the whole animal tests.